The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. Previous work in disorders of consciousness including the postictal state suggests that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) may improve level of arousal. We tested the effects of postictal thalamic CL DBS in a rat model of secondarily generalized seizures elicited by electrical hippocampal stimulation. Thalamic CL DBS was delivered at 100 Hz during the postictal period in 21 female rats while measuring cortical electrophysiology and behavior. The postictal period was characterized by frontal cortical slow waves, like other states of depressed consciousness. In addition, rats exhibited severely impaired responses on two different behavioral tasks in the postictal state. Thalamic CL stimulation prevented postictal cortical slow wave activity but produced only modest behavioral improvement on a spontaneous licking sucrose reward task. We therefore also tested responses using a lever-press shock escape/avoidance (E/A) task. Rats achieved high success rates responding to the sound warning on the E/A task even during natural slow wave sleep but were severely impaired in the postictal state. Unlike the spontaneous licking task, thalamic CL DBS during the E/A task produced a marked improvement in behavior, with significant increases in lever-press shock avoidance with DBS compared with sham controls. These findings support the idea that DBS of subcortical arousal structures may be a novel therapeutic strategy benefitting patients with medically and surgically refractory epilepsy.

SIGNIFICANCE STATEMENT The postictal state following seizures is characterized by impaired consciousness and has a major negative impact on individuals with epilepsy. For the first time, we developed two behavioral tasks and demonstrate that bilateral deep brain stimulation (DBS) of the thalamic intralaminar central lateral nucleus (CL) decreased cortical slow wave activity and improved task performance in the postictal period. Because preclinical task performance studies are crucial to explore the effectiveness and safety of DBS treatment, our work is clinically relevant as it could support and help set the foundations for a human neurostimulation trial to improve postictal responsiveness in patients with medically and surgically refractory epilepsy.

癫痫发作后的姿势状态以意识障碍为特征，并对癫痫患者具有重大的负面影响。先前关于意识障碍（包括姿势状态）的研究表明，丘脑层内中央外侧核（CL）的双侧深脑刺激（DBS）可能会改善觉醒水平。我们在由海马电刺激引起的继发性癫痫发作的大鼠模型中测试了丘脑丘脑CL DBS的作用。丘脑CL DBS在发作期以100 Hz的频率传递给21只雌性大鼠，同时测量其皮质电生理和行为。发作期以额叶皮质慢波为特征，就像其他意识低落状态一样。此外，大鼠在姿势状态下对两种不同的行为任务表现出严重的反应减退。丘脑CL刺激阻止了后皮质的慢波活动，但在自发舔蔗糖奖励任务中仅产生了适度的行为改善。因此，我们还使用压杆式避震/回避（E / A）任务测试了响应。即使在自然的慢波睡眠中，对E / A任务的声音警告做出反应的大鼠也取得了很高的成功率，但在姿势状态下大鼠严重受损。与自发的舔舔任务不同，丘脑CL DBS在E / A任务期间产生了明显的行为改善，与假手术控件相比，DBS避免了杠杆按压震动的发生显着增加。

意义声明癫痫发作后的姿势状态以意识障碍为特征，并对癫痫患者产生重大的负面影响。首次，我们开发了两个行为任务，并证明了丘脑椎板内层中央外侧核（CL）的双侧深脑刺激（DBS）减少了皮质波的活动，并改善了发作期的任务表现。由于临床前任务绩效研究对于探索DBS治疗的有效性和安全性至关重要，因此我们的工作具有临床意义，因为它可以支持并帮助为人类神经刺激试验奠定基础，以改善医学和外科难治性癫痫患者的邮政反应性。